Method of cleaning ophthalmic lenses with alkaline composition

ABSTRACT

A pH controlled protein removal system and method in the substantial absence of (a) enzyme and (b) a surfactantly effective amount of a surfactant is disclosed. The method comprises contacting a substrate with a cleaning composition therefor, which compostion is substantially free of (a) enzyme and (b) surfactantly effective amount of a surfactant, for a period of time at an alkaline pH and removing said substrate from said composition.

This is a divisional of Ser. No. 08/258,909, filed Jun. 13, 1994, whichis a continuation of Ser. No. 07/993, 500, filed Dec. 18, 1992, nowabandoned, which is a continuation of Ser. No. 07/748,603, filed Aug.22, 1991, now abandoned which is a continuation of Ser. No. 07/451,488,filed Dec. 15, 1989, now abandoned.

FIELD OF THE INVENTION

The invention relates to the field of cleaning compositions, morespecifically to cleaning compositions for the removal of protein fromsubstrate, especially polymeric substrates and ophthalmic devices,specifically contact lenses.

BACKGROUND OF THE INVENTION

Cleaning compositions of various types have been known for many years,comprising many different components. Such composition are used tosolubilize, abrade, oxidize, or reduce surfaces in an effort to removeundesirable surface adherents and restore a desired surface. Each typeof surface to be cleaned presents its own characteristics which must betaken into account when choosing an appropriate cleaning compositiontherefor. Polymeric substrates offer particularly problematic issues inchoice of cleanser composition due to the relatively large amounts ofproteins which adhere thereto.

Especially thorny cleaning problems arise when the substrate to becleaned is a contact lens. In addition to the parameters to beconsidered for the polymeric material of the contact lens per se, onemust also take into account that the optical surfaces cannot be scarred,residue must be quickly and easily rinsed away with very small volumesof fluid, tonicity must be in an appropriate range so as not todestabilize the material, the cleaning system has to be non-toxic andnon-allergenic (at least to the extent residue remains or is likely toremain) etc.

Specifically with reference to contact lens cleaning, protein adhesionand build up on the lens, sequestered primarily from tear fluid, hasbeen a persistant and nagging problem. To deal with this difficulty,three general approaches have been attempted. The earliest attempt wasto include an abrasive component, so that upon rubbing the lenstherewith, the adhering protein would be broken up and town away fromthe lens. Compositions of this type include slurries of organiccompounds such as sucrose, dextrose, etc., of inorganic compounds suchas silica, sodium chloride, aluminum oxide, sodium carbonate, etc., ofpolymeric materials such as nylon beads, silicon polymer beads etc., orof other particulate matter such as glass beads.

A second type of attempted solution involved adding a surfactant. Thesurfactant is added to substantially solubilize the adherent protein.Compositions of this type include siloxane surfactants, alkylglycosides,polyalkylene oxy modified silicone etc. Attempts were also made in thecombination of the two types above. Such compositions include Opticleanand Restore.

A third type of attempt to deal with the adherent protein has been toutilize an enzyme to digest the protein.

Of course the protein method can be used alone or in combination withany of the aforementioned methods of dealing with protein deposits.Typical available enzymatic cleaners for contact lenses include papain,subtilisin, pancreatin and other proteases.

While each of these methods has been somewhat successful in proteinremoval, each presents its share of drawbacks. For example, manyabrasives are too harsh for use with contact lenses. Surfactants, inefficacious amounts for their surfactant properties, can irritate theeye terribly. Enzymes which degrade protein must never be placed intothe eye for obvious reasons. Furthermore, the smaller protein fragmentswhich result may be taken up further by the lens material or penetratedeeper into the lens matrix. In addition, enzymes if injected into theenvironment in substantial quantities create a considerableenvironmental hazard.

OBJECTS OF THE INVENTION

One object of the present invention is to provide a cleaner compositionfor use in the removal of protein from a substrate (i.e. contact lens)which avoids the problems of the art as noted above.

Another object of the invention is to provide a simple, yet effectivecleaning regimen for contact lenses and other surfaces.

Still another object of the invention is to provide a means for creatinga cleaning solution in accordance with the preceeding objectives in situby the user thereof.

Yet another object is to provide an environmentally responsibleformulation for removing protein from lenses.

SUMMARY OF THE INVENTION

Surprisingly, these and other objectives of the invention are achievedby a pH controlled cleaning compositions comprising water, a tonicitybuilder and a pH controller, in the substantial absence of (a) an enzymeand (b) protein dissolving efficacious amount of a surfactant and amethod of removing protein therewith from a substrate having proteinthereon comprising contacting said substrate with said composition for atime sufficient to loosen and remove substrate-adhered protein therefromto result in a cleaned substrate and removing said substrate (absent theformerly adhered protein) from said composition.

DETAILED DESCRIPTION OF THE INVENTION

The invention in the case of a contact lens cleaner is directed to asolution having as its only requirements:

(a) water as a carrier;

(b) a tonicity builder in an amount sufficient to result in anapproximately isotonic solution at the conclusion of the dosage regimen;

(c) a pH regulating agent capable of maintaining an alkaline pH in therange of 7.5 to 11.5 in the presence of the other components of thecomposition;

(d) substantially protein digesting enzyme; and

(e) in the absence of a protein dissolving effective amount of asurfactant.

The tonicity builder can be any ionic or non-ionic species which issufficiently soluble to give the appropriate tonicity, which after thecleaning regimen is complete is ocularly acceptable, and which iscompatible with the lens material.

Typical tonicity builders for use in the invention include suitablewater soluble salts compatible with ocular tissue, preferably alkali oralkali earth metal halide, sulfates, nitrates, carbonates, borates, andphosphates, more preferably sodium or potassium chloride. The tonicitybuilder is present in an amount sufficient to provide a tonicity in thefinal solution of the dosage regimen of 50 to 400 mosmole, mostpreferably 250 to 350 mosmole. When non-contact lens cleaning is thedesired use, the tonicity builder may also be absent or in even greateramounts than set forth above.

The pH regulator maintains the pH preferably in the range of 7.5 to11.5, more preferably 8.0 to 10.0, most preferably 8.5 to 9.5 for atleast a period of time of from 10 min. to 24 hrs., preferably 30 min. to8 hrs., more preferably 1 hr. to 6 hrs. or until a pH altering agent isadded to the solution. The pH regulating agent is selected frominorganic or organic bases, preferably basic acetates, phosphates,borates, nitrates, sulfates, tartrates, lactates, carbonates,bicarbonates and mixtures thereof, more preferably basic phosphates,borates, citrates, tartrates, carbonates, bicarbonates and mixturesthereof. Typically, it is present in an amount of 0.001% to 2%,preferably 0.01% to 1%. The pH altering agent may or may not be a partof the initial composition and, when not part of the initialcomposition, may be added after a specified period of time as set forthabove. The pH altering agent is preferably selected from inorganic ororganic acids, more preferably acidic acetates, phosphates, borates,nitrates, sulfates, citrates, tartarates, lactates, carbonates, andbicarbonates, most preferably acidic phosphates, borates, citrates,tartarates, carbonates and mixtures thereof. The pH altering agent ispresent in an amount, when part of the original composition, or added inan amount, when not, which is sufficient to overcome the pH regulatingagent and reset the pH to that desired.

Other typical and suitable ingredients, but not required ingredientsinclude viscosity enhancer, defoaming agent, wetting agent andmicrobicidal agents.

As stated above, the inventive compositions do not contain any enzymesfor the removal of protein. Additionally, the compositions of thepresent invention either contain no surfactants or, if they do, onlyamounts thereof which do not provide any significant protein dissolveproperty. The intent here is to allow inclusion of compounds which havemultiple properties, one of which is as a surfactant in the composition.Such a compound is to be includable within the composition only atproportions which do not provide significant protein dissolvingproperties.

Enzyme, as used in the present context, is intended to mean a catalyticbiological entity capable of degrading protein.

The compositions of the present invention can be formulated in nearlyany conventional manner that would be considered suitable by those ofordinary skill.

Additional excipients typically used in protein removing cleaningcompositions may be added depending on ultimate use compatibility. Suchmaterials include viscosity enhancing agents, lubricants, abrasives,coating agents, disintegrating/dissoluting agent, binders, wettingagents, gildants, fillers, colors, etc. These additional materials aretypically selected from dextrin, starch, sucrose, lactose, maltose,mannitol, sorbitol, dextrose, fructose, xylose, polyethylene glycol,polyethylene monostearates, glyceryl palmitostearate, stearic acid,magnesium stearate, calcium stearate, gelatin, polyvinyl pyrolidone,methylcellulose phthalate, polyethylene glycol. Amylose, alginic acid,effervescent systems (CO₂), sodium - starch glycolate, soypolysaccharides. Gelatin, guar gum, carboxymethylcellulose,hydroxyethylcellulose.

More specifically, the present invention is directed to the removal ofprotein, especially lysozyme (and other proteins typically adhering tocontact lenses, such as IgM, serum IgA, secretory IgA, IgG, lactoferrin,albumin, peroxidase and tear specific prealbumin, from contact lenses,especially soft contact lenses. In the contact lens fields lysozyme(found in tear fluid), deposition on contact lenses and subsequentcleaning of lenses so fouled is a continuous and thorny problem. Mostcontact lenses have polymeric matrix structures which contain multiplenegative sites at neutral or approximately neutral pH. Lysozyme, and asignificant number of other proteins, has an isoelectric point above theusual range of pH in the cleaner used with contact lenses. Specifically,lysozyme has an isoelectric point of about 10-11. Below the isoelectricpoint, the protein has substantial positive charge and hence isattracted to the lens matrix. Enzymes, which cleave the protein intosmaller pieces but do not account for the attractive ionic forces, onlypermit the fragment to permeate still further into the lens matrix,making cleaning even harder.

In the instant invention, the pH of the cleaner is maintained in therange of 7.5 to 11.5, which is near the isoelectric point. Since thelysozyme will have significantly less positive charge and may have a netnegative charge the attractive force of the lysozyme for the lens willdiminish or even be replaced by a weak repulsive force. In this way theprotein contaminant on the lens can be readily removed.

In addition, the present invention offers advantages over the enzymecleaners. First, the present invention does not fragment the adheredprotein so that further migration of protein into the matrix is notincreased. Additionally, as enzymes are themselves proteins, with theenzyme cleaners, there is risk of the lens having residual enzymepresent even after careful rinsing. The present invention has no addedenzyme and therefore is free of this problem. Still further, as enzymescontinue to remain active after disposal, the present, enzyme free,formulations are much more environmentally elegant and suitable thanprior enzyme containing compositions.

Still more specifically, the present invention is directed tocompositions for cleaning protein deposits from contact lenses in theabsence of enzymes and in the absence of a protein dissolving effectiveamount of a surfactant comprising a 250 to 350 mosmole solution at pH7.5 to 11.5 by basic borate or phosphate buffer and sodium chloride.

In a further embodiment, a one step system is contemplated wherein anouter shell carries out the instant invention and a delayed release coreadjusts the pH into a tolerable range from which the lens with minimalrinsing, can be placed directly on the users eye without significantirritation.

The invention method comprises contacting a proteinaccous depositcontaining polymeric material, especially a contact lens, with asolution having a pH between about 7.5 and 11.5, preferably about 8.2and about 10, more preferably about 8.5 to about 9.5, for a period of upto about 24 hours, preferably about 10 min. to about 12 hrs., morepreferably 30 min. to about 8 hrs., most preferably 1 hr. to about 6hrs., and removing the contact lens from such solution. If desired theso cleaned lens may then be rinsed or placed into a soaking solution. Infurther embodiment, the inventive solution is the result of a coating ona core dissolving and after a specified time in which the lens residesin such solution, the core dissolves, whereby the inventive solution istransformed in situ into a type of soaking solution. In such anembodiment, at minimum, the pH is returned to one from which withminimal rinsing direct administration to the eye would be suitable.

The instant invention will be more fully understood by reference to thefollowing illustrative, but non-limiting Examples.

EXAMPLE 1

10 Vifilicon A lenses were soaked for 18-20 hrs. in 0.12% lysozymesolution containing 0.7% sodium chloride, 0.58% boric acid, and 0.05%sodium boratedecahydrate adjusted to pH 7.2 with dilute HCL a-diluteNaOH as needed, Lysozyme deposition was determined by absorbancemeasurement at 280 nm.

The lenses were then placed in one of 5 buffered saline solutions (asset forth in Table I) for 2 hours, rinsed in saline, and absorbance at280 nm was measured again and is reported in Table I

                                      TABLE I                                     __________________________________________________________________________    0.1 M                                                                         sodium                                                                        dihydrogen                                                                             0.1 M                                                                             0.1 M                                                                             0.025 M      ABSORBANCE                                         phosphate,                                                                          HCl,                                                                              NaOH,                                                                             borax,       POST    POST     %      AVERAGE                 pH mL    mL  mL  mL   Nacl    DEPOSITION                                                                            TREATEMENT                                                                             DECREASE                                                                             %                       __________________________________________________________________________                                                          DECREASE                6.0                                                                              50        5.6      SUFFICIENT                                                                            0.858   0.799    7       7                                            TO      0.725   0.681    6                              7.0                                                                              50        29.1     BRING   0.826   0.740    10      8                                            TONICITY                                                                              0.843   0.749    6                              8.0                                                                              50        46.1     TO      0.867   0.676    22     21                                            300     0.828   0.670    19                             9.0      4.6     50   MOSMOL  0.842   0.696    17     15                                                    0.799   0.707    12                             10.0         18.3                                                                              50           0.708   0.540    24     21                                                    0.881   0.733    17                             __________________________________________________________________________

EXAMPLE 2 (COMPARATIVE)

The procedure of Example 1 is followed except that enzymatic cleanersdesignated in Table II, having the given pH values, after tabletdissolution were used instead of the present invention solution.

                                      TABLE II                                    __________________________________________________________________________                       Absorbance         Average                                                    Post  Post  % Decrease                                                                           % Decrease                              Cleaner    Enzyme                                                                              pH                                                                              Deposition                                                                          Treatment                                                                           in Abs in Abs                                  __________________________________________________________________________    Allergan ®                                                                           Papain                                                                              7.7                                                                             0.849 0.668 21     19                                      Enzymatic        7.7                                                                             0.861 0.719 16                                             Contact Lens Cleaner                                                          Alcon      Pancreatin                                                                          6.3                                                                             0.825 0.715 13                                             Opti-Zyme ®  6.4                                                                             0.848 0.647 24                                             Enzymatic Cleaner                                                             Bausch * Lomb                                                                            Subtilisin                                                                          7.1                                                                             0.708 0.624 12                                             Renu ® Effervescent                                                                        7.1                                                                             0.892 0.740                                                Enzymatic Contact                                                             Lens Cleaner                                                                  Allergan   Subtilisin A                                                                        9.1                                                                             0.533 0.458                                                Ultrazyme ™   9.1                                                                             0.617 0.489                                                Enzymatic Cleaner                                                             (in saline)                                                                   __________________________________________________________________________

EXAMPLE III (COMPARATIVE)

The procedure of Example 1 is followed except that Bausch & Lombs ReNuEffervescent Enzymatic Cleaner containing the enzyme subtilisin is addedto the instant invention solution, in the same concentration as inExample 2. This eliminates any confusion due to other materials inExample 2 which are dissimilar to those in Example 1. The results areshown in

                  TABLE III                                                       ______________________________________                                        Absorbance                   Average                                               Post      Post       % Decrease                                                                             % Decrease                                 pH   Deposition                                                                              Treatment  in Abs   in Abs                                     ______________________________________                                        6    0.750     0.677      10        8                                              0.749     0.701       6                                                  7    0.828     0.763       8       10                                              0.736     0.649      12                                                  8    0.674     0.608      10       13                                              0.949     0.794      16                                                  9    0.582     0.514      12       15                                              0.961     0.785      18                                                  10   0.653     0.541      17       14                                              0.700     0.629      10                                                  ______________________________________                                    

We claim:
 1. A method of removing proteinaceous deposits from anophthalmic lens, comprising the steps of:(a) contacting the contact lensan aqueous solution; (b) contacting said aqueous solution with atonicity builder including a water soluble salt compatible with occulartissue; and (c) contacting said aqueous solution with a pH regulator,whereby the pH regulator maintains the pH of the aqueous solutioncontacting the lens from about 7.5 to 11.5 for a cleaning period of 10minutes to 24 hours.
 2. A method of claim 1, wherein said pH regulatoris selected from the group consisting of basic acetates, phosphates,borates, nitrates, sulfates, tartrates, lactates, carbonates,bicarbonates, and mixtures thereof.
 3. A method of claim 1, wherein thecontacting occurs in the substantial absence of protein digesting enzymeand in the substantial absence of a surfactantly-effective amount ofsurfactant.
 4. A method of claim 1, wherein the pH is maintained between8.0 and 10.0 during the cleaning period.
 5. A method of claim 4, whereinthe pH is maintained between 8.5 and 9.5 during the cleaning period. 6.A method of claim 1, wherein the cleaning period is between one and sixhours.
 7. A method of claim 1, further comprising the step ofneutralizing said high pH solution to a pH of about 6.5 to 7.5 aftersaid cleaning period.
 8. A method of removing proteinaceous depositsfrom an ophthalmic lens, comprising contacting said lens with a solutionhaving a pH of 7.5 to 11.5 for a period of time sufficient to clean saidlens.
 9. A method of claim 8, wherein said solution pH is about 8.0 to10.0.
 10. A method of claim 9, wherein said solution pH is about 8.5 to9.5.
 11. A method of claim 9, wherein said period of time is 10 minutesto 24 hours.
 12. A method of claim 9, wherein said period of time is oneto six hours.
 13. A method of claim 8, further comprising the step ofneutralizing said high pH solution to a pH of about 6.5 to 7.5 aftersaid cleaning period.
 14. A method of cleaning ophthalmic lensescomprising contacting an ophthalmic lens with a solution having a pH ofat least 8.5 for a period of time sufficient to clean the lens.
 15. Amethod of claim 14, wherein the pH is between 8.5 and 11.5.